Studies in the Synthesis of Physiologically Important

制备具有生物重要性的天然分子的努力对美国的健康科学非常有价值。首先，这些努力为将开发下一代重要药物的科学家提供了一个特殊的培训场所。其次，这些努力总是为天然产物本身和类似结构类中的化合物提供访问结构活性关系数据的独特手段。第三，这些努力总是导致可用于合成复杂分子的新策略和化学的发展。这份提案描述了三种这样的综合努力。最成熟的是针对一类角鲨烯合成酶抑制剂，称为拟除草剂。在这一领域的努力催生了芳基氧化领域的新化学；提出了这一领域的进一步发展，以及针对重要的钙通道阻滞剂兰诺醇的第二次合成努力。最后，对含有α，β-环氧酮的天然产物的生物学进行了卓有成效的合作研究，旨在提供有关山梨西林类分子的重要生物学信息。

Efforts to prepare naturally occurring molecules of biological importance are extremely valuable to health sciences in the United States. Firstly, these efforts provide an exceptional training ground for scientist who will develop the next generation of important drugs. Second, these efforts always provide a unique means of accessing structure activity relationship data for the natural products themselves and compounds in similar structural classes. Thirdly, these efforts always result in the development of new strategies and chemistry that can be used for the synthesis of complex molecules. This proposal describes three such synthetic efforts. The most mature is directed toward a class of squalene synthase inhibitors known as the phomoidrides. Efforts in this area have spawned new chemistry in the field of aryl oxidation; further developments in this area are proposed along with a second synthetic effort directed toward ryanodol, an important calcium channel blocker. Finally, a fruitful collaborative effort looking at the biology of alpha, beta-epoxy ketone-containing natural products is described that is destined to provide important biological information about molecules in the sorbicillin class.